A new form of latent scrapie virus has been found. This causes a delayed form of scrapie in mice 18 months after inoculation of the newborn mouse. The project will characterize this model. After a latent period of about one year this latent agent is activated to commence the normal incubation period sequence with replication first in the spleen, then in the brain. This project will test a theory of the pathogenesis of latent scrapie by following virus replication and by testing the effects of relevant factors upon it. These will focus upon the possible key role in scrapie virus replication of a lymphoid system cell type, possibly the thymocyte, which matures in the first few days after birth.